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M9490368.TXT
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1994-09-19
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Document 0368
DOCN M9490368
TI Antisense oligodeoxynucleotide phosphorothioate complementary to Gag
mRNA blocks replication of human immunodeficiency virus type 1 in human
peripheral blood cells.
DT 9411
AU Lisziewicz J; Sun D; Weichold FF; Thierry AR; Lusso P; Tang J; Gallo RC;
Agrawal S; Laboratory of Tumor Cell Biology, National Cancer Institute,;
National Institutes of Health, Bethesda, MD 20892.
SO Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7942-6. Unique Identifier :
AIDSLINE MED/94336663
AB Gene-expression modulator 91 (GEM91) is a 25-nt antisense
oligodeoxynucleotide phosphorothioate complementary to the Gag mRNA of
human immunodeficiency virus type 1 (HIV-1). Cellular uptake and
intracellular distribution of GEM91 within cells suggest that this
oligomer is readily available for antisense activity. GEM91 inhibited
HIV-1 replication in a dose-dependent and sequence-specific manner. In a
comparative study, 2 microM GEM91 was as effective as 5 microM
3'-azido-3'-deoxythymidine in blocking virus replication during the
28-day treatment of an HIV-1-infected T-cell line. GEM91 also completely
inhibited (> 99%) the growth of three different HIV-1 isolates in
primary lymphocytes and prevented the cytopathic effect of the virus in
primary CD4+ T cells. Similarly, treatment with GEM91 for 3 weeks of
HIV-1/BaL-infected primary macrophages blocked virus replication. Based
on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in
animals, a clinical trial was started using this compound as an
antisense oligonucleotide drug for the treatment of the acquired
immunodeficiency syndrome.
DE Antigens, CD/BIOSYNTHESIS Antigens, CD4/BIOSYNTHESIS Antigens,
CD8/BIOSYNTHESIS Antiviral Agents/*TOXICITY Base Sequence Biological
Transport Cell Line Cells, Cultured Flow Cytometry Gene Products,
gag/*BIOSYNTHESIS Genes, gag Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY
Kinetics Lymphocytes/CYTOLOGY/DRUG EFFECTS/*MICROBIOLOGY
Macrophages/CYTOLOGY/*MICROBIOLOGY Molecular Sequence Data
Oligonucleotides, Antisense/PHARMACOKINETICS/*TOXICITY RNA,
Messenger/*DRUG EFFECTS Thionucleotides/PHARMACOKINETICS/*TOXICITY
Virus Replication/*DRUG EFFECTS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).